Hereditary Effects

Difference bt teratogenic and hereditary effects

teratogenic = in utero exposure, somatic cells effected

hereditary = genetic exposure, germ cells effected

Is there any statistical evidence of human epidemiological hereditary effects due to contaminants?

no (signal too low)

It’s generally held that protecting against _____ effects will protect against hereditary effects

stochastic

Muller studied the fruit fly by observing mutations on the _ chromosome

X

Muller’s fruit fly experiments showed a _______ response of the mutation rate to radiation dose

linear non-threshold

Muller’s experiments showed the response were independent of dose, indicating that

damage is due to a single hit on a gene

Gene

unit of heredity in a living organism that occupies a specific location on a chromosome, referred to as its locus

In humans, genes vary in size between

a few hundred DNA bases to more than 2 million bases

Human chromosome consist of __ pairs of autosomes present in both sexes plus a pair of XX/XY sex chromosomes

22

Mutation

change in chromosomes, their genes, and/or their DNA

Homologous

paired chromosomes contain parallel genes

Homozygous

paired genes are alike

A completely recessive gene is expressed only if

both corresponding genes of a pair of chromosomes are recessive (or if recessive gene on X chromosome in male)

Some genes permit expression of the _____ counterpart to a varying extent

recessive

What are the categories of mutations?

• Mendelian

• Chromosomal changes

• Multifactorial

Mandelian

caused by mutations in single genes

Autosomal dominant

caused by single mutant gene on one chromosome; expressed in first generation

Autosomal recessive

caused by same mutant gene inherited from both parents; many generations may pass before expressed

Sex-linked

recessive diseases caused by mutations in genes located on the X chromosome; number of mutations need to cause disease based on number of X chromosomes

Chromosomal changes

gross abnormalities in the structure or number of chromosomes (ex: down syndrome is an extra chromosome 21)

About 40% of spontaneous abortions are associated with

chromosomal abnormalities

Multifactorial

diseases known to have genetic component but transmission pattern is not simple Mendelian (no simple relationship between mutation and disease)

Many multifactorial diseases are modified by

environmental conditions

The majority of heritable diseases in the population are

multifactorial

The spectrum for radiation-induced mutations is similar for radiation as it is for

other mutagens

Is there a specific characteristic lesion for ionizing radiation?

no (some people will say dicentrics but those can be caused by a lot of things)

What often dominate radiation-induced mutational spectra of mammalian cells?

deletions and rearrangements

Aberrations are presumably the result of unrepaired clustered DNA damage, so small-scale damage may contribute to

lasting DSB

Does radiation produce bizarre mutations/monsters?

no

Radiation increases the incidence of

the same mutations that occur spontaneously in a given population

Radiation mutations are difficult to study because of

the high natural incidence of the same mutations

Megamouse goal

determine specific locus mutation rates in mouse

Megamouse concluded that the radiosensitivity of different mutations varies by a significant factor of about

35

What was the dose rate observation in the Megamouse study?

• chronic doses induces fewer mutations

• acute dose induces more mutations

• directly contrasts the fruit fly experiments

The Megamouse study proved which sex was more radiosensitive?

male

The Megamouse study said that genetic effects of a given radiation dose can be reduced greatly if

a time interval is allowed between exposure and conception

The estimate of the doubling dose adopted by BEIR V and UNSCEAR 88 is

1 Gy

Doubling dose

dose of radiation, if given uniformly to an entire population, needed to double the spontaneous mutation rate for that population

Epigenetics

study of changes in gene expression of cellular phenotype caused by mechanisms other than changes to underlying DNA sequences (ex: methylation and chromatin remodeling, cellular differentiation, transcription of genes)

Epigenetics can have a profound effect on gene expression, like

silencing the gene

Methylation of cytosine

covalent modification of DNA wherein the H5 hydrogen of the base is replaced by a methyl group

DNA methylation plays a role in

regulating gene expression

DNA methylation is important in

developmental process, genome stability, chromatin compaction, genome defense, etc.

Aberrant methylation

may cause genes to be over/under expressed and has been implicated in many diseases, including cancer (up-regulation of oncogenes and down-regulation of tumor suppressors)

Imprinting

in mammals, father and mother contribute different epigenetic patterns for specific genomic loci in their germ cells (heritable DNA methylation and histone modification)

About __% of autosomal genes in humans are imprinted (expression is from only 1 parental allele with the other allele silenced)

1

The X chromosome contains over ______ genes

1,000

Example of X-inactivation

black/orange fur in cats (whatever X is inactivated, the opposite color appears)